In continuation of our investigations into the RNA transcription processes of animal RNA virus genomes, this proposal concerns an in depth analysis into the in vivo RNA transcription and replication of rhabdoviruses especially vesicular stomatitis (VSV). In particular, the enzymes responsible for its transcription and replication will be characterized, the mechanism and specificity of viral RNA synthesis sought and attempts at selective chemotherapy made using suitable antibiotics. We will also endeavor to develop specific aberrant variant RNA species ('nonsense variants') of the viral genomes using in vitro selection techniques and purified viral enzymes, with the aim of developing their therapeutic value against infected cells, and recognizing that to do so we will need to develop effective ways of introducing such variants into host cells. A genetic map of VSV will be constructed and the relationship of VSV to other members of the rhabdovirus group of viruses sought using RNA hybridization and enzymatic assays.